Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study
- Study type
- Clinical trial
- Study name
- proPSMA
- Design
- Prospective, randomised, two-arm, multicentre study (10 hospitals in Australia)
- Sample size
- 302 men
- Source
- Lancet · 2020
- Trial registration
- ANZCTR12617000005358
In plain words
Before surgery or radiotherapy for high-risk prostate cancer, doctors need to be sure the disease has not spread elsewhere. This study showed that a PET scan using a PSMA tracer is much more accurate than CT and a bone scan (92% vs 65%), gives the patient less radiation, and in most cases helps choose better treatment.
Key results
Treatment arms and regimens
Diagnostic trial without a therapeutic drug: single IV injection of 68Ga-PSMA-11 with an activity of 150 MBq (±50 MBq) according to the trial registration, and PET-CT imaging about 45 to 75 minutes after injection (about 20 minutes on the scanner), as first-line imaging within 21 days after randomisation. Then crossover to conventional imaging within 14 days, unless three or more distant metastases were found. Repeat imaging at 6 months for N1 or M1 patients, or with biochemical or clinical suspicion of residual disease or recurrence.
First-line conventional imaging: contrast-enhanced multidetector CT of the abdomen and pelvis and whole-body bone scan with SPECT/CT after injection of 99mTc-MDP or 99mTc-HDP (the radiotracer activity is not stated in the sources reviewed); then crossover to PSMA PET-CT within 14 days by the same rule.
Source of the regimen details: Published abstract (PubMed 32209449) and the ANZCTR trial registration (ACTRN12617000005358); diagnostic trial without a therapeutic drug
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
302 men aged 18 or older (of 339 assessed; 10 hospitals in Australia, 2017 to 2018) with untreated, biopsy-proven prostate adenocarcinoma, candidates for radical prostatectomy or curative-intent radiotherapy, with at least one high-risk feature: PSA 20 ng/mL or more within 12 weeks before randomisation, Gleason grade group 3, 4 or 5, or clinical stage T3 or higher. Exclusion criteria: any prior prostate cancer treatment; imaging to stage nodal or distant metastases within 8 weeks before randomisation (MRI for T staging or to guide biopsy was allowed); another active malignancy in the past 5 years (except non-melanoma skin cancer or melanoma in situ); and significant sarcomatoid, spindle-cell or small-cell neuroendocrine components.
Endpoints
Primary outcome: accuracy of first-line imaging for detecting pelvic nodal or distant metastases (area under the ROC curve) against a predefined reference standard (pathology, imaging and biochemistry at 6-month follow-up). Secondary outcomes: management change, equivocal findings, radiation exposure and inter-reader agreement.
Safety and side effects
PSMA PET-CT gave lower radiation exposure than CT and bone scan (8.4 versus 19.2 mSv) and fewer equivocal findings (7% versus 23%).
Clinical significance and place in guidelines
proPSMA is the main reason for the gradual replacement of CT and bone scan with PSMA PET for staging high-risk disease. The EAU guideline (2024) regards PSMA PET as the most sensitive method for detecting metastatic spread.
Limitations
The primary outcome was diagnostic accuracy, not survival; it has not yet been shown that treatment based on PSMA PET findings improves long-term patient outcomes; the study was conducted only in Australia, and the reference standard was not always pathology.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.